BMP-7 Signaling and its Critical Roles in Kidney Development, the Responses to Renal Injury, and Chronic Kidney Disease

Manson, Scott R.; Austin, Paul F.; Guo, Qiusha; Moore, Katelynn

doi:10.1016/bs.vh.2015.05.003

Cited by 36 publications

(20 citation statements)

References 202 publications

(281 reference statements)

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“…Over the last decade BMP-7 has emerged as a critical renal protective protein that safeguards the kidney against a variety of stimuli that caused renal injury. 17 , 18 …”

Section: Resultsmentioning

confidence: 99%

Suppression of BMP-7 by histone deacetylase 2 promoted apoptosis of renal tubular epithelial cells in acute kidney injury

Huang

et al. 2017

Cell Death Dis

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Cisplatin, a highly effective and widely used chemotherapeutic agent, has a major limitation for its nephrotoxicity. Currently, there are no therapies available to treat or prevent cisplatin nephrotoxicity. We recently identified a novel strategy for attenuating its nephrotoxicity in chemotherapy by histone deacetylase (HDAC) inhibitors via epigenetic modification to enhance bone morphogenetic protein 7 (BMP-7) expression. Cisplatin upregulated the activity of HDAC2 in the kidney. Inhibition of HDAC with clinically used trichostatin A (TSA) or valproic acid (VPA) suppressed cisplatin-induced kidney injury and epithelial cell apoptosis. Overexpression of HDAC2 promotes CP-treated tubular epithelium cells apoptosis. Chromatin immunoprecipitation assay clearly detected HDAC2 assosiation with BMP-7 promoter. Western blot and immunofluorescence results demonstrated that the expression of BMP-7 was clearly induced by TSA or VPA in vivo and in vitro. Interestingly, administration of recombinant BMP-7 (rhBMP-7) reduced cisplatin-induced kidney dysfunction. Moreover, BMP-7 treatment suppressed epithelial cell apoptosis and small interfering RNA-based knockdown of BMP-7 expression abolished HDAC inhibitors suppression of epithelial cell apoptosis in vitro. Results of current study indicated that TSA or VPA inhibited apoptosis of renal tubular epithelial cells via promoting the level of BMP-7 epigenetically through targeting HDAC2. Hence, HDAC inhibitors could be useful therapeutic agents for the prevention of cisplatin nephrotoxicity.

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“…Over the last decade BMP-7 has emerged as a critical renal protective protein that safeguards the kidney against a variety of stimuli that caused renal injury. 17 , 18 …”

Section: Resultsmentioning

confidence: 99%

Suppression of BMP-7 by histone deacetylase 2 promoted apoptosis of renal tubular epithelial cells in acute kidney injury

Huang

et al. 2017

Cell Death Dis

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“…This gene is a member of the transforming growth factor-β (TGF-β) family, which stimulates the differentiation of osteoblasts from mesenchymal stem cells both in vitro and in vivo [28]. It is also involved in the formation and development of numerous organs [29,30]. So we propose PCK1 and BMP7 as promising candidate genes for BL and HC.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study identifies 22 new loci for body dimension and body weight traits in a White Duroc×Erhualian F2 intercross population

Zhou

Guo

et al. 2017

Asian-Australas J Anim Sci

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ObjectiveGrowth-related traits are important economic traits in the swine industry. However, the genetic mechanism of growth-related traits is little known. The aim of this study was to screen the candidate genes and molecular markers associated with body dimension and body weight traits in pigs.MethodsA genome-wide association study (GWAS) on body dimension and body weight traits was performed in a White Duroc×Erhualian F2 intercross by the illumina PorcineSNP60K Beadchip. A mixed linear model was used to assess the association between single nucleotide polymorphisms (SNPs) and the phenotypes.ResultsIn total, 611 and 79 SNPs were identified significantly associated with body dimension traits and body weight respectively. All SNPs but 62 were located into 23 genomic regions (quantitative trait loci, QTLs) on 14 autosomal and X chromosomes in Sus scrofa Build 10.2 assembly. Out of the 23 QTLs with the suggestive significance level (5×10−4), three QTLs exceeded the genome-wide significance threshold (1.15×10−6). Except the one on Sus scrofa chromosome (SSC) 7 which was reported previously all the QTLs are novel. In addition, we identified 5 promising candidate genes, including cell division cycle 7 for abdominal circumference, pleiomorphic adenoma gene 1 and neuropeptides B/W receptor 1 for both body weight and cannon bone circumference on SSC4, phosphoenolpyruvate carboxykinase 1, and bone morphogenetic protein 7 for hip circumference on SSC17.ConclusionThe results have not only demonstrated a number of potential genes/loci associated with the growth-related traits in pigs, but also laid a foundation for studying the genes’ role and further identifying causative variants underlying these loci.

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“…MMC is a chemotherapeutic agent capable of suppressing cell proliferation and represents an approach to a safer use of iPSCs in cell therapy. Using a nephrogenic cocktail composed of inducing factors [9,[28][29][30], we successfully differentiate hiPSCs into RPCs, which presented morphological characteristics and molecular markers typical of the podocyte lineage. Since podocytes injury or depletion may lead to dysfunction and alterations of the glomerular ltration barrier, and given that these cells cannot be naturally replaced after injury [31,32], we hypothesized that, in vitro differentiation of hiPSCs into podocyte progenitor cells, could be a potential new approach to improve renal function at the end stage of CKD.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

Ribeiro

Lojudice

Fernandes-Charpiot

et al. 2020

Preprint

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Background: Chronic Kidney Disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD.Methods: We transplanted Mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPCs and hiPSCs cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology and immunohistochemistry were evaluated 45 days post-surgery.Results: We successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups.Conclusions: In conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seems to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improve clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD.

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BMP-7 Signaling and its Critical Roles in Kidney Development, the Responses to Renal Injury, and Chronic Kidney Disease

Cited by 36 publications

References 202 publications

Suppression of BMP-7 by histone deacetylase 2 promoted apoptosis of renal tubular epithelial cells in acute kidney injury

Suppression of BMP-7 by histone deacetylase 2 promoted apoptosis of renal tubular epithelial cells in acute kidney injury

Genome-wide association study identifies 22 new loci for body dimension and body weight traits in a White Duroc×Erhualian F2 intercross population

Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

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